I.R.C.C.S. Neuromed, Pozzilli, Italy.
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Schizophr Bull. 2020 Dec 1;46(6):1471-1481. doi: 10.1093/schbul/sbaa074.
Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using a highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found that CA is present in trace amounts in human brain tissue. CA levels were largely reduced in the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication and might, therefore, represent a trait of schizophrenia. Interestingly, systemic treatment with low doses of CA (<1 mg/kg, i.p.) showed robust efficacy in several behavioral tests useful to study antipsychotic-like activity in mice and rats and attenuated MK-801-evoked glutamate release. CA failed to display antipsychotic-like activity and inhibit excitatory synaptic transmission in mice lacking mGlu4 receptors. These findings suggest that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.
肉桂酰基苯丙氨酸（CA）是一种犬尿氨酸代谢物，可激活 mGlu4 代谢型谷氨酸受体。使用高灵敏度的超高效液相色谱/串联质谱（UPLC/MS-MS）方法，我们发现 CA 以痕量形式存在于人脑组织中。精神分裂症患者的前额叶皮层（PFC）中 CA 水平大幅降低。这种降低与年龄、性别、疾病持续时间以及抗精神病药物的持续时间和类型无关，因此可能代表精神分裂症的特征。有趣的是，系统给予低剂量 CA（<1mg/kg，腹腔注射）在几种行为测试中表现出强大的疗效，这些测试可用于研究小鼠和大鼠的抗精神病样活性，并减轻 MK-801 诱发的谷氨酸释放。CA 未显示出抗精神病样活性，也不能抑制缺乏 mGlu4 受体的小鼠的兴奋性突触传递。这些发现表明 CA 是一种有效的内源性抗精神病样分子，而 PFC 中 CA 水平的降低可能导致精神分裂症的病理生理学改变。
